Reliance on glycolysis has been correlated with disease progression in cancer, and as well as a consistent and significant increase in activity of hexokinase, phosphofructokinase and pyruvate kinase. Hypoxia is also a feature of many solid cancers and has been linked to malignant transformation, metastasis and treatment resistance. Furthermore, glycolysis in cancer cells can be enhanced by certain oncogenes through the increased expression of glucose transporters and glycolytic enzymes found on tumor cells.
Malignant gliomas are the most common subtype of primary brain tumors and the deadliest human cancers. In its most aggressive manifestation, glioblastoma multiforme (GBM), the median survival duration for patients ranges from 9 to 12 months, despite maximum treatment efforts. In fact, approximately one-third of patients with GBM their tumors will continue to grow despite treatment with radiation and chemotherapy.
A serious disadvantage of treating glioblastoma is the harmful effects on normal cells and tissue. Mutagenic potential of certain neoplasmic therapies often promotes tumor resistance and can initiate other malignancies. Tumors can also develop resistance to various other treatments, such as anti-angiogenic therapy. A need exists, therefore, for cancer treatments for highly glycolytic cancer cells such as glioblastoma with little or no toxicity towards normal cells.